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Differential Behavioral Effects of Gonadal Steroids in Women with and in Those without Premenstrual Syndrome
Open accessAbstract
BACKGROUND: The symptoms of women with premenstrual syndrome improve in response to suppression of ovarian function, although these women have no evidence of ovarian dysfunction. We undertook a study to determine the role of estrogen and progesterone in this syndrome. METHODS: We first studied the effect of ovarian suppression with leuprolide, an agonist analogue of gonadotropin-releasing hormone, or placebo on symptoms in 20 women with the premenstrual syndrome. Ten women whose symptoms improved during leuprolide treatment were given estradiol and progesterone in a double-blind, crossover design, each for four weeks, during continued leuprolide administration. Women without premenstrual syndrome (normal women) participated in a similar protocol. Outcomes were assessed on the basis of daily self-reports by the patients and biweekly rater-administered symptom-rating scales. RESULTS: The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo. The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration. CONCLUSIONS: In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.
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“Prior evidence suggests another possibility, namely that individual differences in responsiveness to cycle shifts could be larger in magnitude compared to cycle shifts themselves [37].”
From Menstrual cycle effects on cognitive performance: A meta-analysis (2025) · cites this paper as [37]
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Metadata
- Authors
- Schmidt, P. J., Nieman, L. K., Danaceau, M. A., Adams, L. F., & Rubinow, D. R.
- Affiliations
- National Institutes of Health (US)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (US)
- National Institute of Mental Health (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1998-01-22
- Volume
- 338
- Issue
- 4
- Pages
- 209-216
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2046110224
- Cited by
- 765
- References
- 28
- Citations by year
- 2026: 30 · 2025: 38 · 2024: 26 · 2023: 27 · 2022: 31 · 2021: 28 · 2020: 21 · 2019: 24 · 2018: 24 · 2017: 26 · 2016: 32 · 2015: 23 · 2014: 24 · 2013: 31 · 2012: 31
- FWCI
- 29.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Upsher-Smith
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- premenstrual syndrome, premenstrual dysphoric disorder, leuprolide, GnRH agonist, ovarian suppression, estradiol, progesterone, estrogen, symptom recurrence
- MeSH terms
- Adult, Double-Blind Method, Emotions, Estradiol, Female, Humans, Gonadotropin-Releasing Hormone, Middle Aged, Premenstrual Syndrome, Progesterone, Leuprolide, Cross-Over Studies, Hot Flashes
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